This research attempts to increase the diagnostic capability of an already useful, non-invasive and objective clinical test of retinal function, the electroretinogram (ERG) by taking advantage of the information that has been learned about the functional organization of the retina from single cell neurophysiology in primates and other animals. The approach uses carefully controlled spectral stimuli, either separately or interacting with one another, on spectrally selective backgrounds, both in full-field presentation and coupled to an electronic computer in order to increase both the sensitivity and rapidity for identifying specific responses. This method will provide a means of isolating and identifying the action spectrum and ERG waveform of the blue sensitive cone mechanism, of the midspectral cone mechanism, possibly including that of the so called red and green sensitive cone mechanisms of human color vision. It will use these separate responses in double flash experiments to investigate synaptic interactions between these mechanisms, known to exist in primate retina, between the blue cone system and midspectral cones on the one hand and between the midspectral (red and green) cones on the other. Response changes due to such interactions must reflect unique and hitherto unexplored function with the synaptic layers of the human retina. It will use negative pulses (of darkness) to separate off- from on-responses of these separate cone systems and thereby provide information on parallel channels, including, most likely, on- and off-center bipolar systems, which represent these cone mechanisms in the inner retinal layers. It will use pattern evoked ERGs in which both the energy and the wavelength across the borders of each pattern can be independently controlled in order to separate the activity of ganglion cells from that of more inner retinal layers, to separate collor-opponent from non-color opponent channels and possibly X from Y mechanisms in the human ERG. The methodology will be used to examine selective genetic defects of the human retina such as achromats, protanopes, deuteranopes and several unusual pedigress showing unique retinal abnormalities presumably of the blue sensitive cone mechanism, that have been discovered at Columbia over the past three years.